What are currently the best ways to treat cannabis overconsumption symptoms such as anxiety? New research may lead to better options to treat these symptoms.

Emergency room visits for cannabis overdose are reportedly on the rise. There is little chance of an actual medical emergency due to the safety profile of THC and other cannabinoids. However, users who have taken too much can experience acute anxiety, which may lead them to think that their health is in danger.

“The most common reason someone goes to the ER for a marijuana reaction is anxiety” -Dr. Larry Bedard, former president of the American College of Emergency Physicians.

Other symptoms of cannabis or THC overconsumption include a rapid heart rate, hallucinations, confusion, and paranoia. The duration of symptoms depends on the dose and how it was taken. Unfortunately, the dose is hardest to control with edibles, and this is also when effects last the longest.

As more states legalize recreational cannabis, we can expect that more people inexperienced in edibles (or who are exposed to a wider array of products) may accidentally take too much.

So what are the current treatment options if you ingest too much THC?

[Flickr/ 125o4]

Benzodiazepines and Sedatives

The recommended protocol for someone presenting in the ER with cannabis overconsumption is to treat with a sedative such as a benzodiazepine and observe until symptoms subside.

Those with access to benzodiazepines at home may end up using these if they feel that they are having symptoms of anxiety after taking cannabis. You should take these with caution since there may be additive or synergistic sedative effects between THC and benzodiazepines. The dose needed to reduce anxiety may be much lower if you have consumed cannabis than if you haven’t. Due to dangerous drug interactions, benzodiazepines should never be used if other sedatives, alcohol, or opiates have been taken.

A number of naturally occurring terpenes (myrcene, limonene, pinene, and others) have sedative effects via a benzodiazpine-like mechanism. In this case, the possible synergism with THC could be helpful for boosting the sedative effect of these weaker molecules.

Although alcohol also has sedative properties, combining alcohol and cannabis (especially with high doses) often leads to extreme dizziness and nausea. Therefore, drinking is not a recommended strategy for dealing with a cannabis overdose.

Although sedatives may reduce the anxiety caused by cannabis overconsumption, there is one large drawback. You will remain intoxicated (and may be even more so). Driving or doing anything requiring energy or coordination is completely out of the question. Time must be allowed for the effect of both drugs to wear off.

[Pexels]

Rimonabant and CB1 Receptor Antagonists

This may surprise you – but a near perfect antidote to cannabis overconsumption already exists. It has already been tested in thousands of people and at one point was an approved drug in Europe.

This drug is called rimonabant – it is an antagonist (actually an inverse agonist) of the cannabinoid CB1 receptor. In other words, it binds the CB1 receptor (without activating it) and blocks THC from binding and activating the receptor. It essentially works the same way as naloxone does at the mu opioid receptor to reverse heroin overdoses.

Rimonabant was developed as an anti-obesity medication, but it was pulled from the market in 2008 after serious psychiatric side effects were observed. However, those side effects only occurred with chronic dosing. It appears to be very safe after a single dose, and this is all that would be needed to rescue someone from cannabis overconsumption.

A clinical study has already shown that rimonabant blocks the acute effects of cannabis in humans. Although they did not specifically test blocking the effects of a cannabis overdose, there is little reason to think that it would not be effective.

One key advantage of a CB1 receptor antagonist is that you would quickly regain more normal cognitive function. Unlike sedatives, you would not become even more drowsy and have to wait a long time for the effects to wear off.

I doubt there is much financial incentive for a company to get this drug reapproved for cannabis overconsumption. Perhaps the NIH (which already has a sizeable budget for cannabinoid research) could step up to the plate? Or we could get this crowdsourced? These scenarios all seem unlikely to me, but anything is possible.

[July 2017 update] It has recently come to my attention that a natural compound called olivetol may also act as a CB1 receptor antagonist. A company called Undoo has filed a patent for its use in THC overconsumption and created a product for this use. However, there are still no available studies to assess its efficacy.

Cannabidiol and Negative Allosteric Modulators

Cannabidiol (CBD) is another molecule in the same cannabinoid group as THC. It may hold promise for treating cannabis overdose. I know it sounds funny at first – treating cannabis overdose with more cannabinoids.

CBD is a weak antagonist and negative allosteric modulator (or NAM) of THC at the CB1 receptor. What this means is that CBD can “turn down the volume” on THC activation of the CB1 receptor without directly blocking THC from binding the CB1 receptor.

My analysis of studies that combined THC and CBD showed that CBD does not block the actual high of THC. However, it can help with certain side effects such as anxiety and paranoia.

In fact, a company called CannaSafety has filed a patent for the treatment of cannabis overdose with a formulation containing CBD. They have launched this as a commercial product, although CBD is also available from many different sources.

The advantages of CBD are that it is safe, widely available, and arguably legal. Absorption may be relatively slow if taken orally, which could be tough for people who need immediate relief. However, there is also the option to vaporize CBD oil, which can provide a very rapid effect.

Synthetic NAMs of the CB1 receptor have been created, but so far none have advanced to testing in humans.

Pregnenolone and Signaling-Specific Inhibitors

In 2014, there was a huge step forward in our understanding of how our brains regulate cannabinoid signaling. Scientists found that pregnenolone, a naturally occurring steroid precursor, was a natural modulator of the CB1 receptor.

In response to CB1 receptor activation, our brains start synthesizing pregnenolone, which then blocks further CB1 receptor activation. When synthesis of pregnenolone was blocked in mice, all of the effects of THC were amplified.

Activation of the CB1 receptor stimulates multiple pathways of intracellular signaling. Interestingly, pregnenolone is able to block a specific signaling pathway, and thus is considered a “signaling-specific” inhibitor.

Pregnenolone is freely available to be sold in the US as a dietary supplement. So you would think that this would be an obvious choice for cannabis overdose. However, there are challenges with the absorption and stability of pregnenolone taken orally. Since little pregnenolone is absorbed and it is rapidly converted to other steroids, very little pregnenolone makes it to your brain intact.

One way to circumvent this is to take pregnenolone via the intranasal route. Intranasal administration resulted in high brain levels of pregnenolone and improved memory in mice. However, whether intranasal pregnenolone is effective for cannabis overdose in humans has not yet been demonstrated. If proven effective, this would be an excellent treatment option.

Aelis Farma is developing compounds that have the same action as pregnenolone at the THC receptor, but have good bioavailability and stability. If one of these compounds is approved as a drug (which is still uncertain and a long way off), it could be a future option for treating cannabis overdoses.

Conclusion on Treatment of Cannabis Overconsumption

Current options for treating the symptoms of cannabis overconsumption are limited to sedatives, CBD, and some other natural products. In the future, we may have other CB1 receptor blockers or modulators available that will be effective in reducing anxiety and other effects of overconsumption.

[Featured image: Flickr/ Alessandra]

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Last modified: July 12, 2017

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